Platelet Activating Factor (PAF) derived from rabbit leukocytes is a powerful inducer of platelet aggregation and granular secretion, and is believed to be a mediator of allergic reactions. Recently PAF and 1-alkyl-2-acetoyl-sn-glycero-3-phosphocholine (1-alkyl-2-acetoyl-GPC) were shown to have identical physicochemical properties and biological activities; the studies indicate PAF is 1-alkyl-2-acetoyl-GPC (Demopoulos et al., J. Biol. Chem. 254, 9355, 1979). Concurrently, 1-alkyl-2-acetoyl-GPC was shown to possess potent antihypertensive activity (Blank et al., Biochem. Biophys. Res. Commun. 90, 1194, 1979). This compound is one of the most biologically active materials ever described. We propose to determine what pathway(s), which tissues, and which cell types of the blood and vascular system are responsible for the catabolism of PAF. Our approach is initially to incubate (14C)PAF with whole blood, isolated cells and tissue slices, and to extend these investigations to in vivo studies to determine which cell types and tissues most actively catabolize PAF. Our studies will focus on three key enzyme activities: a soluble acetyl hydrolase, which removes the acetate of 1-alkyl-2-acetoyl-GPC and yields 1-alkyl-2-lyso-GPC; lysophospholipase D, a microsomal enzyme that removes basic groups from 1-alkyl-2-lyso-GPC and appears specific for alkyl-linked lipids; and the alkyl cleavage enzyme that cleaves the ether bond itself. By comparing the labeled metabolites of PAF in various cells and the kinetics of the enzymes, we expect to find what pathway(s), enzyme activities, and cells are responsible for the catabolism of PAF. We also propose to: 1) investigate mechanisms by which the enzymes can be activated and inhibited and thus control the level of PAF in tissues, 2) purify and characterize the acetyl hydrolase, and 3) purify lysophospholipase D and to establish unequivocally that it is specific for alkyl-linked lysophospholipids.